Oxidative Stress In Various Diseases Research Articles

Rapid and reliable quantification of urinary malondialdehyde by HILIC-MS/MS: A derivatization-free breakthrough approach

BackgroundThe development of fast analytical methods is crucial for the research, discovery, and confirmation of crucial biomarkers. Furthermore, the implementation of fast analytical strategies contributes to efficient and time-effective procedures. In this sense, analysis of malondialdehyde (MDA) has become an important tool for understanding the role of oxidative stress in various diseases and for evaluating the efficacy of therapeutic interventions. ResultsA rapid and robust liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) has been developed to determine endogenous amounts of malondialdehyde (MDA) in human urine without any associated derivatization reaction. MDA was separated in 4 min through a Urea-HILIC column and was analyzed using a triple quadrupole mass spectrometer in negative electrospray ionization mode. With a 50-fold dilution as the only sample pretreatment after alkaline hydrolysis, no matrix effect was present, which allowed for a fast and simple quantification by means of an external standard calibration with a limit of detection of 0.20 ng mL−1. The whole methodology was validated by analyzing unspiked and spiked urine samples from ten healthy individuals and comparing with the results obtained by the standard addition method. MDA was detected in all cases, with natural concentrations varying from 0.11 ± 0.03 to 0.31 ± 0.03 mg g−1 creatinine. Accuracies were found to be satisfactory, ranging from 95 % to 101 %. The proposed method also exhibited good repeatability and reproducibility (RSD<15 %) for four quality control levels. SignificanceThe main significance of this method is the avoidance of a derivatization reaction for the determination of urinary MDA, this constituting a step forward when compared with previous literature. This breakthrough not only streamlines time analysis to less than 5 min per sample but also results in a more robust procedure. Consequently, the method here developed could be applied to subsequent future research involving the determination of MDA as a lipid peroxidation biomarker, where simple, rapid, and reliable methods could represent a significant improvement.

Laquinimod attenuates oxidative stress-induced mitochondrial injury and alleviates intervertebral disc degeneration by inhibiting the NF-κB signaling pathway

BackgroundLow back pain (LBP) caused by intervertebral disc degeneration (IVDD) is a significant global health concern. It is necessary to investigate the underlying pathological mechanisms leading to IVDD and develop precise treatment strategies for this condition. Considering the well-established anti-inflammatory properties and ability to reduce oxidative stress in various diseases, for the first time we aim to explore the potential of Laquinimod in alleviating IVDD. MethodsWe used hydrogen peroxide (H2O2) to simulate the oxidative stress microenvironment in IVDD, and Laquinimod for intervention purposes. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assay were used to measure the expression levels of inflammatory cytokines, catabolic enzymes, and markers of extracellular matrix (ECM) synthesis in nucleus pulposus (NP) cells. In addition, dichlorofluorescin-diacetate (DCFH-DA) and JC-1 fluorescent probes, flow cytometry analysis, and qRT-PCR were used to measure mitochondrial function and apoptosis in NP cells under conditions of oxidative stress. An acupuncture-induced rat model of IVDD was established to further evaluate the efficacy of Laquinimod in alleviating IVDD in vivo. ResultsOur findings showed that Laquinimod significantly reduced the oxidative stress-induced inflammatory response in NP cells, downregulated the expression of catabolic enzymes, and markedly enhanced ECM degradation by inhibiting the NF-κB signaling pathway. The administration of Laquinimod concurrently improved the mitochondrial functional state and reduced apoptosis in NP cells. Additionally, in vivo experiments in rats showed that Laquinimod significantly alleviated acupuncture-induced IVDD. ConclusionsCollectively, the findings of this study provide new insights into the therapeutic potential of Laquinimod as a treatment for oxidative stress-induced IVDD.

Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides.

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.

Esculentoside A ameliorates DNCB-induced atopic dermatitis by suppressing the ROS-NLRP3 axis via activating the Nrf2 pathway.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence. Inflammation and oxidative stress are strongly associated with AD progression. Esculentoside A (EsA) inhibits inflammation and oxidative stress in various diseases. However, whether EsA mitigates AD by suppressing inflammation and oxidative stress remains unknown. A mouse model of AD was constructed by the induction of 1-chloro-2,4-dinitrochlorobenzene (DNCB). The mechanism of EsA and its effects on AD symptoms, pathology, inflammation and oxidative stress were investigated through histopathological staining, enzyme-linked immunosorbent assay, blood cells analysis, colorimetric measurement and western blot analysis. EsA improved the clinical symptoms and increased clinical skin scores in AD mice. Skin thickening of the epidermis and dermal tissues and the mast cell numbers in AD mice were reduced with the EsA treatment. EsA decreased the relative mRNA level of thymic stromal lymphopoietin, interleukin (IL)-4, IL-5 and IL-13; the serum concentrations of immunoglobulin E (IgE) and IL-6; and the numbers of white blood cells (WBC) and WBC subtypes, including basophil, lymphocytes, eosinophil, neutrophil and monocytes in DNCB-induced mice. DNCB caused higher levels of oxidative stress, which was reversed with the administration of EsA. Mechanically, EsA upregulated the expression of Nrf2 but downregulated the level of NLRP3 inflammasome in AD mice. The inhibitor of Nrf2 significantly recovered the EsA-induced changes in the NLRP3 inflammasome proteins in DNCB-treated mice. Therefore, EsA improved the clinical and pathological symptoms, inflammation and oxidative stress experienced by DNCB-induced mice and was involved in the inactivation of NLRP3 inflammasome by activating Nrf2.

Rola lekarza rodzinnego i ginekologa w opiece nad kobietą

The risk of many gynecological diseases can be remarkably reduced by making several changes in patients’ lifestyles. In this respect, emphasize the importance of family doctor care. Even if only through education on hygiene, proper diet, and physical activity. From the point of view of prevention and treatment, it is essential to understand the factors contributing to inflammation and oxidative stress in various diseases. Moreover, clinicians should know the patient’s body’s defense mechanisms. Undoubtedly, it is also crucial to ensure universal access to women’s reproductive health services, including in rural areas. The importance of early detection of neoplastic lesions at any age is emphasized, especially in genetically predisposed individuals with an increased risk of cancer. In this case, more frequent medical examinations are recommended from the patient’s childhood.

Potential Functions of the tRNA-Derived Fragment tRF-Gly-GCC Associated With Oxidative Stress in Radiation-Induced Lung Injury.

ObjectiveTransfer RNA-derived small RNAs (tsRNAs) are a novel type of non-coding RNA with various regulatory functions. They are associated with oxidative stress in various diseases, but their potential functions in radiation-induced lung injury (RILI) remain uncertain.MethodsTo explore the role of tsRNAs in RILI, we used X-rays to irradiate human bronchial epithelial cells and examined the expression profile of altered tsRNAs by RNA sequencing and bioinformatics analysis. Sequencing results were verified by qRT-PCR. tsRNA functions were explored using several methods, including CCK-8, reactive oxygen species (ROS) assays, cell transfection, and western blotting.ResultsEighty-six differentially expressed tRNA-derived fragments (tRFs) were identified: 64 were upregulated, and 22 were downregulated. Among them, the regulation of tRF-Gly-GCC, associated with oxidative stress, may be mediated by the inhibition of cell proliferation, promotion of ROS production, and apoptosis in the occurrence and development of RILI. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the underlying molecular mechanism may involve the PI3K/AKT and the FOXO1 signaling pathways.ConclusionOur findings provide new insights into the molecular mechanisms underpinning RILI, advancing the clinical prevention and treatment of this disease.

MicroRNA-7a-5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c-JUN pathway.

The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA-7a-5p (miR-7a-5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR-7a-5p in DPN. DPN cell model was constructed with high-glucose-induced RSC96 cells. Cell apoptosis and viability were detected by flow cytometry analysis and cell counting kit-8 (CCK-8) assay respectively. The apoptosis and Jun N-terminal kinase (JNK)/c-JUN signalling pathway-related proteins expression were detected by Western blotting. The intracellular calcium content and oxidative stress levels were detected by flow cytometry and reagent kits. Mitochondrial membrane potential was evaluated by tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) staining. The targeting relationship between miR-7a-5p and voltage-dependent anion-selective channel protein 1 (VDAC1) was determined by RNA pull-down assay and dual-luciferase reporter gene assay. The streptozotocin (STZ) rat model was constructed to simulate DPN in vivo. The paw withdrawal mechanical threshold (PTW) was measured by Frey capillary line, and the motor nerve conduction velocity (MNCV) was measured by electromyography. MiR-7a-5p expression was decreased, while VDAC1 expression was increased in HG-induced RSC96 cells and STZ rats. In HG-induced RSC96 cells, miR-7a-5p overexpression promoted cell proliferation, inhibited apoptosis, down-regulated calcium release, improved mitochondrial membrane potential and repressed oxidative stress response. MiR-7a-5p negatively regulated VDAC1 expression. VDAC1 knockdown improved cell proliferation activity, suppressed cell apoptosis and mitochondrial dysfunction by inhibiting JNK/c-JUN pathway activation. MiR-7a-5p overexpression raised PTW, restored MNCV and reduced oxidative stress levels and nerve cell apoptosis in STZ rats. MiR-7a-5p overexpression ameliorated mitochondrial dysfunction and inhibited apoptosis in DPN by regulating VDAC1/JNK/c-JUN pathway.

Sulforaphane Attenuates Chronic Intermittent Hypoxia-Induced Brain Damage in Mice via Augmenting Nrf2 Nuclear Translocation and Autophagy.

Obstructive sleep apnea–hypopnea syndrome (OSAHS), typically characterized by chronic intermittent hypoxia (CIH), is associated with neurocognitive dysfunction in children. Sulforaphane (SFN), an activator of nuclear factor E2-related factor 2 (Nrf2), has been demonstrated to protect against oxidative stress in various diseases. However, the effect of SFN on OSAHS remains elusive. In this research, we investigated the neuroprotective role of SFN in CIH-induced cognitive dysfunction and underlying mechanisms of regulation of Nrf2 signaling pathway and autophagy. CIH exposures for 4 weeks in mice, modeling OSAHS, contributed to neurocognitive dysfunction, manifested as increased working memory errors (WMEs), reference memory errors (RMEs) and total memory errors (TEs) in the 8-arm radial maze test. The mice were intraperitoneally injected with SFN (0.5 mg/kg) 30 min before CIH exposure everyday. SFN treatment ameliorated neurocognitive dysfunction in CIH mice, which demonstrates less RME, WME, and TE. Also, SFN effectively alleviated apoptosis of hippocampal neurons following CIH by decreased TUNEL-positive cells, downregulated cleaved PARP, cleaved caspase 3, and upregulated Bcl-2. SFN protects hippocampal tissue from CIH-induced oxidative stress as evidenced by elevated superoxide dismutase (SOD) activities and reduced malondialdehyde (MDA). In addition, we found that SFN enhanced Nrf2 nuclear translocation to hold an antioxidative function on CIH-induced neuronal apoptosis in hippocampus. Meanwhile, SFN promoted autophagy activation, as shown by increased Beclin1, ATG5, and LC3II/LC3I. Overall, our findings indicated that SFN reduced the apoptosis of hippocampal neurons through antioxidant effect of Nrf2 and autophagy in CIH-induced brain damage, which highlights the potential of SFN as a novel therapy for OSAHS-related neurocognitive dysfunction.

Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases.

Oxidative stress is a major contributor to the pathogenesis of various inflammatory diseases. Accumulating evidence has shown that oxidative stress is characterized by the overproduction of reactive oxygen species (ROS). Previous reviews have highlighted inflammatory signaling pathways, biomarkers, molecular targets, and pathogenetic functions mediated by oxidative stress in various diseases. The inflammatory signaling cascades are initiated through the recognition of host cell-derived damage associated molecular patterns (DAMPs) and microorganism-derived pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). In this review, the effects of PRRs from the Toll-like (TLRs), the retinoic acid-induced gene I (RIG-I)-like receptors (RLRs) and the NOD-like (NLRs) families, and the activation of these signaling pathways in regulating the production of ROS and/or oxidative stress are summarized. Furthermore, important directions for future studies, especially for pathogen-induced signaling pathways through oxidative stress are also reviewed. The present review will highlight potential therapeutic strategies relevant to inflammatory diseases based on the correlations between ROS regulation and PRRs-mediated signaling pathways.

Vagus Nerve Stimulation Attenuates Early Traumatic Brain Injury by Regulating the NF-κB/NLRP3 Signaling Pathway

Background Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Oxidative stress, inflammation, and apoptosis are vital pathophysiological features post-TBI. Objectives Research has shown that vagus nerve stimulation (VNS) can attenuate oxidative stress in various diseases. However, the critical role of VNS in TBI is still not completely understood. This study investigated the protective effects and potential mechanism of VNS on TBI. Methods Male Sprague-Dawley rats were randomized into 3 groups: sham, TBI, and TBI + VNS. The TBI model was induced in rats by the free-fall drop method. The vagal nerve trunk was separated, and VNS was performed after establishing the TBI model. Results The results showed that VNS significantly ameliorated tissue damage, neurological deficits, and cerebral edema, compared with the sham VNS group. Additionally, VNS alleviated oxidative stress, inflammation, and apoptosis in the pericontusive cortex of rats after TBI. VNS also significantly suppressed expression of the nuclear factor-κB (NF-κB) protein in the nucleus and activation of the nucleotide-binding domain–like receptor protein 3 (NLRP3) inflammasome. Conclusions Taken together, the present study indicates that VNS may attenuate brain damage after TBI by inhibiting oxidative stress, inflammation, and apoptosis, possibly through the NF-κB/NLRP3 signaling pathway.

Proline improves cardiac remodeling following myocardial infarction and attenuates cardiomyocyte apoptosis via redox regulation

At present, ischemic heart failure (HF) caused by coronary heart disease (CHD) has a high morbidity and mortality, placing a heavy burden on global human health. L-Proline (Pro), a nonessential amino acid and the foundation of proteins in the human body, was found to be protective against oxidative stress in various diseases. However, the role of Pro in cardiovascular disease (CVD) remains unclear. In vivo, adult mice were subjected to left anterior descending (LAD) artery ligation for 4 weeks with or without Pro treatment. In vitro, H9c2 cardiomyocytes were pretreated with or without Pro, followed by treatment with hydrogen peroxide (H2O2) (200 μM) for 6 and 12 h. Our data showed that Pro metabolism was disturbing after myocardial infarction (MI). Pro treatment improved cardiac remodeling, reduced infarct size, and decreased oxidative stress and apoptosis in mouse hearts after MI. Pro inhibited the H2O2-induced increase in reactive oxygen species (ROS) in H9c2 cells and protected against H2O2-induced apoptosis. Mechanistically, by RNA sequencing (RNA-seq) and pathway analysis, Pro was shown to exert a protective effect through H2O2 catabolic processes and apoptotic processes, especially oxidative phosphorylation (OXPHOS). Taken together, our findings suggested that Pro protects against MI injury at least partially via redox regulation, highlighting the potential of Pro as a novel therapy for ischemic HF caused by CHD.

Cucurbita argyrosperma seed extract ameliorating oxidative stress in H9c2 cardiomyocytes through suppression of intracellular reactive oxygen species production

Background: Oxidative stress induced by the excessive reactive oxygen species (ROS) generation is involved in the pathogenesis of various diseases. Methanol extract from Cucurbita argyrosperma (CM) was used to test for antioxidant and antioxidative stress. Materials and Methods: The radical scavenging potential was determined using eight different in vitro assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical, β-carotene-linoleic acid, chelating activity, ferric reducing antioxidant power (FRAP), hydroxyl radical, nitric oxide (NO) radical, and superoxide anion radicals, palmitate (PA) on H9c2 cells, and H2O2-induced cell damage on H9c2 cardiomyocytes. Results: CM showed antioxidant activity with DPPH radical values of EC507.6 ± 5.38 mg/mL, β-carotene-linoleic acid EC50 of 279.4 ± 36.32 mg/ml, chelating activity EC50 of 301.2 ± 9.78 mg/ml, FRAP EC50 of 101.3 ± 3.10 mg/ml, hydroxyl EC50 of 42.6 ± 8.6 mg/mL, superoxide EC50 of 50.6 ± 8.66 mg/ml, NO EC50 of 101.2 ± 19.74 mg/ml, and ABTS EC50 of 13.2 ± 4.9 mg/ml. The methanol extract preincubation decreases the intracellular ROS induced by H2O2 and PA in H9c2 cells in a concentration-dependent manner. The methanol extract could also protect H9c2 cells and inhibit the activity of xanthine oxidase, malondialdehyde, and lactate dehydrogenase which increases cell viability, heme oxygenase-1, glutathione/oxidized glutathione, superoxide dismutase-1, catalase, and GSH-Px? levels. Conclusions: The finding suggests that methanol extract can protect the oxidative stress-induced cardiomyocyte damage through ROS regulation and can be used as a therapeutic agent for the improvement of oxidative stress in various diseases. Abbreviations used: ABTS radical: 2,2'-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid; CAT: Catalase; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DMSO: Dimethyl sulfoxide; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DPPH: 1,1-diphenyl-2-picrylhydrazyl; DCFH-DA: 2',7'-dichlorofluorescin diacetate; FRAP: Ferric reducing antioxidant power; GSH: Glutathione; GSH-Px: Glutathione peroxidase; HO-1: Heme oxygenase-1; OH−: Hydroxyl; LDH: Lactate dehydrogenase; LOOH: Lipid peroxide; LOO•: Lipid peroxyl; MDA: Malondialdehyde; NO: Nitric oxide; GSSG: Oxidized glutathione; O2−1: Oxygen; O3 Ozone; PA: Palmitate; RO2−: Peroxyl; PBS: Phosphate-buffered saline; ROS: Reactive oxygen species; O2•: Superoxide; SOD: Superoxide dismutase; TFs: Total flavonoids; TP: Total phenolic; TCA: Trichloroacetic acid; XO: Xanthine oxidase.

Liquid Chromatographic Determination of Malondialdehyde in Plasma Samples After Liquid–Liquid Microextraction

Background: Malondialdehyde is a product of lipid peroxidation of polyunsaturated fatty acids in foods and biological samples and widely used as biomarker of oxidative stress in various diseases. We describe the validation of a new microextraction-LC-UV method for the determination of malondialdehyde (MDA) in the form of 2,4-dinitrophenylhydrazine (DNPH) derivatization in plasma samples. Objective: A new microextraction technique called vortex and N2 assisted liquid-liquid microextraction has been developed for the determination MDA in plasma samples. Method: The DNPH-derivatized MDA was extracted into ethyl acetate as an extraction solvent and measured by LC-UV at 310 nm after evaporation of ethyl acetate and re-dissolving in mobile phase composed of 0.2% acetic acid–acetonitrile (50:50; v/v). This method validated according to U.S. Food and Drug Administration guidelines. Results: The limit of detection of MDA was 0.038 µmol L-1 (2.74 µg L-1) and the intra and interday relative standard deviations were in the range of 3.8-5.0% and 5.5-9.4%, respectively for different concentrations of MDA. Conclusion: A precise and valid method to measure MDA as DNPH derivatization in plasma samples using LC was proposed. Keywords: Malondialdehyde, 2, 4-dinitrophenylhydrazine, vortex assisted liquid liquid microextraction, N2 assisted liquid liquid microextraction, validation, samples.

Polyphenols protect against age-associated apoptosis in female rat cochleae.

Dietary antioxidants, polyphenols, have been found to be beneficial in protecting against the generation of oxidative stress in various diseases associated with aging. Age-related hearing loss (AHL) is the number one neurodegenerative disorder on our aged population. Sprague-Dawley rats divided into five groups according to their age (3, 6, 12, 18 and 24months old) and treated with 100mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to measure caspase activities (-3, -8 and -9), caspase-3 gene expression, ATP levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage) and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9 in cochlea were observed with age and this effect was attenuated by polyphenol treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after administration of polyphenols, while Bax and p53 levels protein decreased. Oral supplementation with polyphenols also reduces DNA oxidative damage of cochlear cell. Treatment with polyphenols inhibits the activation of age-related apoptotic signaling by decreasing oxidative stress inside the rat cochlea.

Oxidative stress--a key emerging impact factor in health, ageing, lifestyle and aesthetics.

Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention.

Role of oxidative stress in various diseases: Relevance of dietary antioxidants

Oxidative stress plays important role in the pathophysiology of various diseases. Oxidative stress is caused in body due to an imbalance between the activities of endogenous pro-oxidative enzymes. Cellular antioxidants are known to change their redox state and they can be targeted for destruction, regulate oxidative processes involved signal transduction, effect gene expression and the pathways of cell proliferation and death. Oxidants and antioxidants play an important role in maintaining a balance between free radicals produced by metabolism or derived from environmental sources and the antioxidant system of the body. A natural antioxidant system exists in the biological systems which is responsible for prevention of damage by pro-oxidants. Impaired endogenous antioxidant system results in accumulation of free radicals, which not only induces lipid peroxidation but also imposes severe stress on the body leading to many diseases such as Alzheimer’s disease, Parkinson disease, Diabetic neuropathy, various cardiovascular diseases. Antioxidant system may be intrinsic or extrinsic. Intrinsic involves body own neutralizing systems and extrinsic antioxidant involves dietary supplements that are taken in the form of food like vitamin C, vitamin E and beta carotene that can be gained from the fruits and vegetables for the prevention and management of diseases induced by free radicals.

Hydrogen improves neurological function through attenuation of blood-brain barrier disruption in spontaneously hypertensive stroke-prone rats.

BackgroundEnhanced oxidative stress occurs in spontaneously hypertensive stroke-prone rats (SHRSP), and is important in blood–brain barrier (BBB) disruption. Hydrogen can exert potent protective cellular effects via reduction in oxidative stress in various diseases. The present study investigated whether long-term hydrogen treatment can improve neurological function outcome in the SHRSP model, and the effects of hydrogen on BBB function, especially the oxidative stress and the activity of matrix metalloproteinases (MMPs) in this model. Fifty-six animals were randomly assigned to 2 groups and treated as follows: SHRSP treated with hydrogen-rich water (HRW) (HRW group, n = 28); and SHRSP treated with regular water (control group, n = 28). The effect of HRW on overall survival and neurological function, and the effects of HRW on reactive oxygen species, BBB function, and MMP activities were examined.ResultsHRW treatment improved neurological function and tended to improve overall survival but without significant difference. The numbers of bleeds and infarcts were lower in the cortex and hippocampus in the HRW group. The HRW group exhibited a significantly lower number of 8-hydroxy-2'-deoxyguanosine-positive cells and vessels of extravasated albumin in the hippocampus compared with the control group. MMP-9 activity was reduced in the hippocampus in the HRW group compared with the control group.ConclusionsThe present study suggests that ingestion of HRW can improve neurological function outcome in the SHRSP model. This beneficial effect may be due to attenuation of BBB disruption via reduction in reactive oxygen species and suppression of MMP-9 activity in the hippocampus.

Antioxidant and methyl donor effects of betaine versus ethanol-induced oxidative stress in the rat liver

Oxidative stress is one hypothesis for the association of ethanol consumption with cardiovascular, cerebrovascular, and liver diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the rat liver. A total of 32 male Sprague–Dawley rats were divided into four equal groups. The control group received normal saline. The ethanol group was administered ethanol (4 g/kg). The betaine group received betaine [1.5 % (w/w) of the total diet], and the betaine plus ethanol group (Bet. & Eth.) were administered with betaine; after 120 min, the rats received ethanol. All of the treatments were applied for 2 months via gavage. Elevation of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were observed in the betaine-treated groups. Thiobarbituric acid reactive substances (TBARS, an indicator of lipid peroxidation) concentration also decreased in the betaine-treated rats as compared to the ethanol group. There was also a significant reduction in plasma total homocysteine (tHcy) concentration in the betaine and Bet. & Eth. groups as compared to the ethanol-treated rats. In contrast, ethanol treatment in rats resulted in significant lower antioxidant enzyme activities (GPx and SOD), and indicated lipid peroxidation to the liver, as monitored by the elevation in TBARS level. Administration of ethanol to rats also induced toxicity in their liver, as shown by the histopathological findings, whereas betaine could suppress liver damages in the Bet. & Eth. group. Overall, oral pretreatment with betaine significantly prevented ethanol-induced oxidative stress and hyperhomocysteinemia via increasing antioxidant enzyme activities and decreasing tHcy concentration. Thus, betaine may be recommended as a therapeutic agent for patients with liver damages induced by oxidative stress in various diseases.

Urinary 8-hydroxydeoxyguanosine correlate with hallucinations rather than motor symptoms in Parkinson’s disease

BackgroundOxidative stress is causally associated with the pathogenesis of Parkinson’s disease (PD). Oxygen generates a large amount of reactive oxygen species (ROS). ROS including hydroxyl radicals and H2O2 react with guanine residues in DNA and produce 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG serves as a biomarker for oxidative stress in various diseases. MethodWe investigated urinary 8-OHdG levels in 61 PD patients and 28 normal subjects to evaluate the correlation with various clinical features. We quantified disease severity using the Unified Parkinson’s Disease Rating Scale for motor symptoms (UPDRS part 3), the Mini-Mental State Examination (MMSE) for mental function, and the Tottori University Hallucination Rating Scale (TUHARS) for quantifying hallucinations. ResultsThere were significant correlations between 8-OHdG and all the examined parameters, but the partial correlation coefficients excluding contributions of all the other parameters showed that only TUHARS and UPDRS part 3 are significantly related to 8-OHdG. In particular, TUHARS correlates best with urinary 8-OHdG levels. ConclusionThe significant correlation between urinary 8-OHdG levels and hallucinations but not with dementia suggests that hallucinations are likely to have unique but unidentified mechanisms that lead to excessive production of 8-OHdG.

Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseases.

Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses.